This cross-national study was funded in April, 1986, to test the hypotheses: 1) that there is a genetically mediated "lesser variant" of autism defined by mental retardation, language delay, reading disability, and social deficits, which is more common in family members of autistic proband than of Downs syndrome proband; 2) that the lesser variant is found less often in family members of autistic proband who had suffered prenatal injury; and 3) that the lesser variant would be differently defined in families of high IQ proband (as language delay, reading and social deficits) than low IQ proband (mental retardation). Based on 18 months of data collection, and a preliminary analysis of 42 autism families and 16 DS families, it seems highly likely that a lesser variant exists, but is defined somewhat differently than we had hypothesized. 1) Family members of autistic proband are distinguished from the DS controls by social deficits, as measured by oddity of vocal and facial expression and by certain semantic and pragmatic language deficits. 2) Relatives of autistic proband more often had diagnoses of affective disorder and anxiety disorders. 3) We have not seen mental retardation in tested relatives of this autistic sample with IQs above 30, and relatives' reading levels are so far compatible with the subjects' IQs. IQ in relatives was related to proband IQ, and may be independent of the lesser variant. We propose in this application to complete the collection of our sample; to add a set of families ascertained through very low IQ proband in an attempt to detect any aggregation of cognitive deficits in relatives of autistic subjects; to better define the lesser variant by a formal, blind analysis of relatives' semantic and pragmatic language; and to merge the Baltimore and London data sets for a detailed genetic analysis. We also propose to explore the relationship of serotonin levels to the presence of the lesser variant; and finally, to collect a set of autism families that are informative for linkage analysis.